부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.gene.2007.04.011 Byline: Guiyu Lou, Yuping Li, Bin Chen, Min Chen, Jian Chen, Rongxia Liao, Yan Zhang, Yuangzhon Wang, Dujin Zhou Keywords: Farnesoid X receptor; Hepatic nuclear factor 1[alpha]; Promoter analysis Abbreviations: ChIP, Chromatin Immunoprecipitation; EMSA, Electrophoresis Mobility shift and Supershift Assay; FXR, Farnesoid X Receptor; HNF1[alpha], Hepatic Nuclear Factor 1[alpha]; RACE, Rapid Amplification of cDNA Ends; BA, bile acid. Abstract: The farnesoid X receptor (FXR) is a bile acid (BA)-activated nuclear receptor that plays a major role in the regulation of BA and lipid metabolism. Although modulation of FXR expression has been reported, the mechanisms underlying the regulation of human FXR are yet unclear. Functional assays showed that the -150/+29 nucleotides region from the first nucleotide at the Exon I is the minimal promoter of the human FXR gene by the technique of serial deletion and point mutants of the 5'-flanking region. Chromatin immunoprecipitation analysis and electrophoretic mobility shift assay revealed that hepatic nuclear factor 1[alpha] (HNF1[alpha]) interacted with the region. Co-transfection of the promoter with HNF1[alpha] expression vectors enhanced promoter activity of FXR gene. Over-expression of HNF1[alpha] up-regulated FXR expression in HepG2 cells. These data indicate that (a) the identified HNF1[alpha] binding site serves as a positive regulatory sequence, (b) the binding site is functionally active both in vivo and in vitro, and (c) the transcription factor HNF1[alpha] that binds to this site plays an important role in the regulation of human FXR promoter activity. Author Affiliation: Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China Article History: Received 19 November 2006; Revised 13 March 2007; Accepted 9 April 2007 Article Note: (miscellaneous) Received by A.J. van Wijnen